新型口腔分散片中盐酸溴己辛及相关杂质含量测定方法的建立与验证

IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY
M. Strozik, M. Strzebońska, Katarzyna Skiba, Wiktor Tatara
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引用次数: 1

摘要

盐酸溴己辛(BRX)作为一种有效药物成分被广泛应用于治疗呼吸道感染的口服溶液和片剂中。然而,由于(3RS)-6,8-二溴-3-环己基-3-甲基-1,2,3,4-四氢喹唑啉-3-ium(被欧洲药典指定为杂质E)的存在,BRX注册过程所要求的现行法规的履行可能构成挑战。为了克服这一问题,开发了一种新型的BRX或分散片(ODT),其化学稳定性得到了改善,含有低水平的杂质e。本文详细阐述了BRX的分析方法和该产品中相关杂质的测定。在ICH II区和III区加速(ACC)、中间(INT)和长期(LT)条件下测试了产品的稳定性。降解物E是检测到的最常见杂质。在INT和LT条件下储存的样品中,仅观察到杂质略有增加,BRX含量略有下降,但结果并未超过预先建立的接受标准。在ACC条件下储存的样品中,已知杂质增加,包括降解剂E,降解剂B和n -氧化物。值得注意的是,即使在产品的保质期三年后,降解E的水平仍然低于0.2%,这对应于BRX相关杂质的ICH识别阈值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Development and validation of the analytical methods for determination of bromhexine hydrochloride and related impurities in novel orodispersible tablets
Bromhexine hydrochloride (BRX) is widely applied as an active pharmaceutical ingredient of oral solutions and tablets for the treatment of the infections of the respiratory tract. However, fulfillment of the present regulations, required for the registration process of BRX, might constitute a challenge, due to the occurrence of (3RS)-6,8-dibromo-3-cyclohexyl-3-methyl-1,2,3,4-tetrahydroquinazolin-3-ium, specified as impurity E by European Pharmacopeia. To overcome this issue, a novel BRX orodispersible tablets (ODT) with improved chemical stability were developed that contain low level of impurity E. Herein the analytical methods, elaborated for the determination of BRX and the related impurities in this product are presented. Stability of the product was tested at accelerated (ACC), intermediate (INT) and long-term (LT) conditions for ICH zones II and III. The degradant E was the most common impurity detected. In the samples stored in INT and LT conditions only a slight increase in the impurities and a slight drop in the assay of the BRX was observed, however the results did not exceed the pre-established acceptance criteria. In the samples stored at ACC conditions, an increase of the known impurities, including degradant E, degradant B and N-oxide, was noted. Noteworthily, even after three years of the product’s shelf-life, the level of the degradant E is still below 0.2 % which corresponds to the ICH identification threshold for the BRX related impurities.
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来源期刊
CiteScore
0.80
自引率
0.00%
发文量
74
审稿时长
6-12 weeks
期刊介绍: The international journal of the Polish Pharmaceutical Society is published in 6 issues a year. The journal offers Open Access publication of original research papers, short communications and reviews written in English, in all areas of pharmaceutical sciences. The following areas of pharmaceutical sciences are covered: Analysis, Biopharmacy, Drug Biochemistry, Drug Synthesis, Natural Drugs, Pharmaceutical Technology, Pharmacology and General. A bimonthly appearing in English since 1994, which continues “Acta Poloniae Pharmaceutica”, whose first issue appeared in December 1937. The war halted the activity of the journal’s creators. Issuance of “Acta Poloniae Pharmaceutica” was resumed in 1947. From 1947 the journal appeared irregularly, initially as a quarterly, then a bimonthly. In the years 1963 – 1973 alongside the Polish version appeared the English edition of the journal. Starting from 1974 only works in English are published in the journal. Since 1995 the journal has been appearing very regularly in two-month intervals (six books a year). The journal publishes original works from all fields of pharmacy, summaries of postdoctoral dissertations and laboratory notes.
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